Regeneron Reports Promising Amyloidosis Trial Results

Regeneron Pharmaceuticals reported encouraging early-stage results from a Phase 1/2 clinical trial evaluating Lynozyfic (linvoseltamab) in patients with relapsed or treatment-resistant systemic amyloid light chain (AL) amyloidosis, a rare and potentially fatal blood disorder for which no approved therapies currently exist after first-line treatment failure.

The company said results from the LINKER-AL2 trial will be presented at the 2026 annual meeting of the American Society of Clinical Oncology (ASCO), highlighting what researchers described as unexpectedly strong hematologic response rates in previously treated patients.

Systemic AL amyloidosis is a rare hematologic disease caused by abnormal plasma cells that produce toxic light chain proteins. These proteins accumulate in organs such as the heart and kidneys, forming amyloid deposits that can lead to progressive organ damage and life-threatening dysfunction.

Current first-line treatment typically involves a four-drug regimen combining daratumumab, bortezomib, cyclophosphamide and dexamethasone. However, treatment options become extremely limited once patients relapse, become refractory to therapy or fail to achieve adequate responses.

Lynozyfic, a BCMAxCD3 bispecific antibody already approved for certain patients with relapsed or refractory multiple myeloma, is now being investigated as a single-agent therapy in systemic AL amyloidosis. The ongoing LINKER-AL2 trial evaluates fixed-duration Lynozyfic monotherapy in adults who have previously received at least one treatment and are classified as second-line-plus patients.

In preliminary findings, all 20 patients enrolled in the study achieved meaningful hematologic responses. Among patients receiving the lower 80 mg dose, 100% achieved at least a very good partial response, while 71% reached hematologic complete response (CR). In the higher 240 mg cohort, every patient achieved complete response.

Researchers also reported rapid reductions in involved free light chain proteins, which normalized by day 15 of treatment, suggesting Lynozyfic rapidly eliminated the plasma cells responsible for producing harmful proteins. Median time to hematologic complete response was reported at 47 days.

Notably, investigators observed evidence of organ improvement, including kidney and cardiac responses. Among evaluable patients, 73% experienced improved renal function and 50% demonstrated cardiac improvement based on biochemical markers. No participants experienced major organ deterioration during follow-up.

Hans Lee, director of myeloma research at the Sarah Cannon Research Institute and an investigator in LINKER-AL2, described the findings as remarkable given that standard first-line therapies historically produce substantially lower complete response rates in untreated patients. He emphasized the lack of approved treatment options for relapsed or refractory systemic AL amyloidosis and said the rapid and deep responses seen with linvoseltamab support continued investigation.

The safety profile of Lynozyfic was broadly consistent with expectations for bispecific antibody therapies. All patients experienced at least one treatment-emergent adverse event, with severe events occurring in 65% of participants. The most common side effects included cytokine release syndrome, neutropenia and infusion-related reactions.

Infections were reported in 85% of patients, though all resolved, according to Regeneron. Investigators also reported one mild case of immune effector cell-associated neurotoxicity syndrome that resolved during treatment.

Two deaths occurred during the study. One patient in the higher-dose group who had achieved complete response experienced sudden death in the setting of cardiac amyloidosis, while another patient in the lower-dose group with pre-existing coronary artery disease died following ventricular fibrillation shortly after a coronary stent procedure, which investigators considered unrelated to Lynozyfic.

The Phase 2 registrational portion of LINKER-AL2 is ongoing, with hematologic complete response serving as the primary endpoint. Regeneron emphasized that Lynozyfic remains investigational for systemic AL amyloidosis and has not yet been evaluated or approved by regulators for this indication.